This revised K01 Mentored Research Career Development Award resubmission will provide the training necessary for Dr. Avalos to establish an independent research program focused on understanding determinants of maternal depression to inform and develop targeted prevention and treatment interventions for high-risk populations. Research from the basic sciences and epidemiology suggest two promising areas for developing prevention interventions and possibly for adjunctive treatment to current pharmacotherapy for maternal depression are nutrition and genetics. In this award she proposes to expand her background in reproductive and perinatal epidemiology by focusing her training and research aims on nutritional and genetic factors in relation to maternal depression. She proposes mentored training through coursework and tailored tutorials in nutrition, depression and genetics. The prevalence of maternal depression ranges from 6-12% for antepartum depression (APD) and 15%-20% for postpartum depression (PPD). Limitations with current treatment options argue for research to understand determinants of maternal depression for the purpose of developing safe and effective interventions. Research suggests a link between folate and depression. The significance of folate in maternal depression is underscored by increased needs during pregnancy and research indicating inadequate dietary folate intake by pregnant women, despite fortification of the food supply and supplementation. The Recommended Daily Allowance for folate was not established for depression, and it is not known what levels may impact depression or if there are certain women who may be more vulnerable due to obesity or genetics. The first research aim will examine whether dietary folate intake and serum folate levels in early pregnancy impact the risk of maternal depression. Dr. Avalos will also explore whether obese women are particularly vulnerable to the impact of folate on maternal depression. The second aim is to evaluate genetic variations of the folate metabolic pathway in relation to PPD. The role of obesity will again be determined. To address these aims, Dr. Avalos will link survey data and EMR data for two studies in Kaiser Permanente Northern California's (KPNC) Research Program on Genes, Environment and Health. The first study is a pregnancy cohort of 1555 women without depression at baseline who completed a Food Frequency Questionnaire and of whom a subsample gave a blood sample. EMR data will be used to ascertain screening and diagnostic information on APD and PPD. The second study includes 3458 women (655 with PPD and 2803 without PPD) who participated in the Genetic Epidemiology Research in Adult Health and Aging cohort which has been genotyped. KPNC's Division of Research is an ideal environment for conducting the proposed research given the extensive EMR databases, access to a large diverse membership, and internationally- recognized investigators. The proposed training and research plan are crucial for providing a platform for Dr. Avalos to compete successfully for R01 funding to become a leading researcher in maternal depression.